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Selective Serotonin Reuptake Inhibitors and Initial Oral Contraceptives for the Treatment of PMDD: Effective But Not Enough

  • Uriel Halbreich

Selective serotonin reuptake inhibitors (SSRIs) are almost unanimously considered to be very efficacious and the first line of pharmacologic treatment for premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS). There is a need to examine if this is actually the case. More recently, combined oral contraceptives (COCs) have been pursued due to their ovulation suppression effects. Their effects on PMS/PMDD should be further examined as well.


For this review of the literature from 1990 to the present, MEDLINE, PsychLit, and Cochrane controlled trials register were searched. Randomized, double-blind, placebo-controlled clinical trials of SSRIs and COCs (N>20) that report the rate of responders and not just percent improvement in severity of symptoms were selected for study. The data extraction were the percentage or number of responders as reported by the original authors.


In many studies, only mean improvement in severity was reported. In all studies, the main inclusion criterion was meeting criteria for PMDD; this has not, however, been an outcome measure. However, only 16 reports that provided actual rate of responders could be included. The percentage of non-responders (100% minus active medication) to SSRIs and COCs was found to be higher than the reported percentage of women who responded to active medication (response rate to an SSRI or COC minus the response rate to placebo).


In the majority of larger-scale studies, once the placebo effect is accounted for, the percentage of women who respond to SSRIs or COCs is actually less than the percentage of women who do not respond at all. SSRIs provide an important step forward in the treatment of PMDD and PMS. COCs provide a different option, still, ~40% of women with PMDD do not respond to SSRIs. Treatment with a currently approved COC does not substantially improve the percentage of responders. Therefore, additional alternative targeted treatment modalities need to be developed.

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CNS Spectrums
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